Escherichia coli is a normal inhabitant of human gastro-intestinal (GI) tract, however, some E. coli strains are pathogenic. Enterohaemorrhagic E. coli (EHEC) target the small and large bowels and can cause haemorrhagic colitis and HUS (haemolytic uraemic syndrome). STEC is an abbreviation for Shiga-toxin producing E. coli. EHEC strains are STEC strains. Shiga-toxin (Stx) acts on the lining of the blood vessels and the vascular endothelium. The toxin penetrates into endothelial cells. When inside the cell, Stx inactivate protein synthesis leading to the death of the cell. The vascular endothelium has to continually renew itself, so this killing of cells leads to a breakdown of the lining and to hemorrhage. The first response is commonly a bloody diarrhea.
The toxin is effective against small blood vessels, such as found in the digestive tract, the kidney, and lungs, but not against large vessels such as the arteries or major veins. A specific target for the toxin appears to be the vascular endothelium of the glomerulus in the kidneys. Destroying these structures leads to kidney failure and the development of the often deadly and frequently debilitating HUS. Food poisoning with Shiga toxin often also has effects on the lungs and the nervous system.
A large number of serotypes of STEC isolated from humans is known. From studies in the USA and Canada examining human STEC infections, 50-80% were identified as being caused by E. coli O157:H7. 30 to 50% are caused by non-O157 STEC. Although E. coli O157:H7 has been most commonly identified as the cause of STEC infection, isolation of non-O157 STEC strains from clinical cases, outbreaks and environmental sources has been increasing (Posse et al., FEMS Microbiol Lett. 2008; 282(1):124-31; Possé et al., J. Appl. Microbiol. 2008; 105(1):227-35). A study at the Center for Disease Control and Prevention showed that from 1983-2002 approximately 70% of non-O157 STEC infections in the United States were caused by strains from one of six major serogroups, namely O26, O45, O103, O111, O121 and O145 (Brooks et al., 2005). Virulence factors for non-O157 STEC include, but are not limited to, production of the shiga-like toxins 1 and/or 2 (Stx1, Stx2) and intimin (eae). USDA-FSIS (United States Department of Agriculture (USDA) and Food Safety and Inspection Service (FSIS)) defined the so-called “Big 7” STEC panel: O26, O45, O103, O111, O121 and O145 serotypes. These are considered as most dangerous STEC serotypes (“adulterants”). EHEC serotypes are generally classified using the O antigen which is a part of the lipopolysaccharide layer, and the H antigen that is flagellin.
Prevention of EHEC or reducing contamination of food with EHEC requires, according to the WHO, control measures at all stages of the food chain, from agricultural production on the farm to processing, manufacturing and preparation of foods in both commercial establishments and household kitchens. As to industry, the WHO recommends that the number of cases of disease might be reduced by various mitigation strategies for ground beef (for example, screening the animals pre-slaughter to reduce the introduction of large numbers of pathogens in the slaughtering environment). Good hygienic slaughtering practices reduce contamination of carcasses by faeces, but do not guarantee the absence of EHEC from products. Education in hygienic handling of foods for workers at farms, abattoirs and those involved in the food production is essential to keep microbiological contamination to a minimum. So far, the only effective method of eliminating EHEC from foods is to introduce a bactericidal treatment, such as heating (e.g. cooking, pasteurization) or irradiation (see: http://www.who.int/mediacentre/factsheets/fs125/en/).
Treatment of EHEC infections in humans is difficult. A multitargeted approach is generally recommended including general supportive measures, anti-platelet and thrombolytic agents and thrombin inhibitor, selective use of antimicrobials, probiotics, toxin neutralizers and antibodies against key pathogenic pathway elements (Goldwater et al., BMC Medicine 2012, 10:12).
Most of the above mentioned methods of preventing EHEC or reducing contamination with EHEC are methods that are essentially independent from a particular pathogenic bacterium or from a particular serotype of EHEC. This has the advantage that little prior knowledge of the specific EHEC serotype in question is necessary before counter-measures are taken. However, the above mentioned methods of preventing EHEC or reducing contamination with EHEC such as heating or irradiation are not always applicable or change the treated good or food in undesirable ways. Other methods may have turned out non-effective with a particular patient. There is therefore a need for further methods of preventing or treating EHEC infections or methods for reducing or preventing contamination of objects with EHEC.
It is an object of the invention to provide methods for preventing or treating EHEC infections such as food-borne EHEC infections. It is another object to provide methods for preventing or reducing contamination of objects, notably, food with EHEC. It is a further object to provide methods for preventing or treating EHEC infections and/or methods for reducing contamination of objects with EHEC, that are effective against a wide range of EHEC serogroups such as the Big 7 or Big 6 groups of serotypes.